As an approach to the study of eukaryotic gene regulation, the expression and structure of genes associated with human erythroid differentiation will be examined. A specific restriction fragment from cloned genomic DNA will be used to probe the structure and metabolism of delta globin mRNA, a normal adult species expressed at a low level. Embryonic globin epsilon and zeta gene structure will be studied by cloning and sequencing the corresponding cDNA and genomic DNA, using as starting material mRNA obtained from an inducible human erythroleukemia cell line (K562). As a more general approach, non-globin mRNA from hemin-induced K562 cells and from reticulocytes will be used as a template to make cDNA, which will be cloned and screened for inducibility during erythroid differentiation. Clones containing inducible sequences will be used as probes for studying the pattern of induction of the corresponding mRNA species, and for isolating the corresponding genomic fragments for a study of possible flanking region homologies. An attempt will be made to identify clones containing sequences coding for two well-characterized erythrocyte proteins, carbonic anhydrase and glycophorin.